Benzyloxycarbonylamino acid

Benzyloxy-4-isopropyl(or 4-terf-butyl)-4-methyl-5(4//)-oxazolones 780 have been prepared from an A-benzyloxycarbonylamino acid 779 using l-(3-dimethyl-aminopropyl)-3-ethylcarbodiimide hydrochloride (EDAC HCl) as the cyclization agent (Scheme 7.237). Treatment of 780 with tetramethylfiuoroformamidinium hexafiuorophosphate (TFFH) has shown that they are possible intermediates in the fluorination of a-methyl-a-alkyl amino acids by TFFH. 

AVal residues can be synthesized by the condensation method or by the N-chlorination/ dehydrochlorination method. 77,149 In the condensation method, either benzylcarbamate or a benzyloxycarbonylamino acid amide is condensed with 3-methyl-2-oxobutanoic acid in benzene using 4-toluenesulfonic acid as a catalyst to obtain Z-AVal or Z-Xaa-AVal dipeptides. 150 In this case it is not possible to elongate the chain from the N-terminus because the... 

As shown above, a combination of ( )-7V-benzyloxycarbonylamino acid (Z-amino acid) and ( )-ephedrine is a successful model resulting in four diastereomer in high yield and optical purity from the racemic acid and base. However, in general, the yield of crystals obtained per crystallization is usually small. 

Figure 13 Optical resolution of V-benzyloxycarbonylamino acid (A) and ephedrine (B) by preferential crystallization...

Di- and oligo-peptides with a terminalo-aminophosphonous acid residue have been prepared by coupling with N-hydroxy succinimide esters of N-benzyloxycarbonylamino acids or peptides. 

When tosylamino or phthaloylamino carboxylic acids are warmed for a short time at 80-85° with an excess of CHCl2OCH3, the corresponding acid chlorides are formed in good yield. However, the acid chlorides formed as primary product from <%-(benzyloxycarbonylamino) acids and SOCl2 or an excess of CHCl2OCH3 split off benzyl chloride smoothly, giving A-(carboxy-amino) acid anhydrides1122 which are important intermediates in peptide synthesis. 

Benzyloxycarbonylamino acids are important for peptide synthesis since, as is well-known, the acyl group is readily removed by hydrogenolysis 575 an example of the preparation of such an amide is therefore provided ... 

Protection of carboxyl groups. Trimethylsilylethyl esters, —COOCH2-CHaSiCCHala, can be prepared from N-benzyloxycarbonylamino acids and this reagent with DCC in the presence of pyridine (65 95% yield). The esters are stable under usual conditions of peptide synthesis, but are readily cleaved by fluoride ion, preferably by fetra-n-butylammonium fluoride in DMF. ... 

A-Benzyloxycarbonylamino acids and 3-pyridinol form 3-pyridyl esters in the presence of dioyclohe lcaibodiiinide. The esters in ethyl acetate are treated with an amino acid ethyl ester hydrochloride and triethylamine to give peptides... 

Path D Hydantoin formation. In certain circumstances hydantoins can be formed from P-tosyloxy-N-benzyloxycarbonylamino acid amides in basic media (273). This reaction can probably be avoided by choice of less drastic conditions. 

JCS2689) and 5-bromomethylpyrimidine (458) and diethyl benzyloxycarbonyl-aminomalonate (459) give initially, diethyl a-benzyloxycarbonylamino-a-(pyrimidin-5-ylmethyOmalonate (460) which can be degraded to 2-amino-3-(pyrimidin-5 -yl)propionic acid (461) (65JHCl>. 

Q, 9/3,9n/3)]-9-(Benzyloxycarbonylamino)-6-oxoperhydropyrido[2,l-Z)][l, 3]thiazine-4-carboxylic acid was obtained from the methyl ester by treatment with 2 N LiOH in MeOH at 0°C for 4.5 h. The carboxyl group was coupled with amino esters. The 9-(benzyloxycarbonylamino) group was deprotected by treatment with a 1 1 mixture of TFA and CH2CI2 at room temperature and the amino group was acylated with an amino acid (97MIP4, 98USP5710129). 

Preparation of L-(-)-y-Benzyloxycarbonylamino-a-Hydroxybutyric Acid L-(-)-7-amino-o-hydroxybutyric acid (7.4 g, 0,062 mol) was added to a solution of 5.2 grams (0.13 mol) of sodium hydroxide in 50 ml of water. To the stirred soiution was added dropwise at 0 -5°C over a period of 0.5 hour, 11.7 grams (0.06B mol) of carbobenzoxy chloride and the mixture was stirred for another hour at the same temperature. The reaction mixture was washed with 50 ml of ether, adjusted to pH 2 with dilute hydrochloric acid and extracted with four BO ml portions of ether. The ethereai extracts were combined, washed with a small amount of saturated sodium chloride solution, dried with anhydrous sodium sulfate and filtered. The filtrate was evaporated in vacuo and the resulting residue was crystallized from benzene to give 11.6 grams (74%) of colorless plates MP 78.5° to 79.5°C. 

Preparation of N-Hydroxysuccinimide Ester of L-(-) y-Benzyloxycarbonylamino-a-Hydroxy-butyric Acid A solution of 10.6 grams (0,042 mol) of L-(-)-7-benzyloxycarbonylamino-o-hydroxybutyric acid and 4.8 grams (0.042 mol) of N-hydroxysuccinimide in 200 ml of... 

L-(-)-7-benzyloxycarbonylamino-o -hydroxybutyrylI -6 -carbobenzoxykanamycin A was dissolved in 40 ml of 50% aqueous dioxane and a small amount of insoluble material was removed by filtration. To the filtrate was added 0.8 ml of glacial acetic acid and 1 gram of 10% palladium-on-charcoal and the mixture was hydrogenated at room temperature for 24 hours in a Parr hydrogenation apparatus. The reaction mixture was filtered to remove the palladium catalyst and the filtrate was evaporated to dryness in vacuo. 

Aminoalkylphosphonic acids are analogues of natural a-aminocarboxylic acids and are designated by generally accepted three-letter abbreviations for the amino acid residue followed by a superscript P. For example, 1-aminoethylphosphonic acid, which is related to alanine, is abbreviated as Alap. Diphenyl [l-(benzyloxycarbonylamino)ethyl]phosphonate, is abbreviated as Z-Alap(OPh)2. The l-aminoalkylphosphonic acids have modest water solubility, which significantly increases in strong acidic and alkali solution. They are not soluble... 

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